A biomimetic strategy is proposed to develop a new class of adhesives for orthopedic medicine, particularly joint fractures with multiple bone fragments. The adhesive is modeled after a natural underwater adhesive secreted by a marine tubeworm to glue together broken bits of seashells and sand grains. The natural glue is comprised of several proteins with simple repetitive sequences and significant quantities of divalent metal ions. The key features of the glue proteins will be copied with inexpensive, easy to manufacture synthetic polymers. The objectives are: 1.) To quantitatively correlate adhesive effectiveness (a convolution of bond strength, setting/curing kinetics, deliverability, and degradability) with formulation variables and delivery methods. This will be accomplished by mechanical testing on the micro and macro scales. 2.) To optimize the synthetic bone adhesive by fine tuning the structures and chemical properties of the mimetic copolymers. This will be accomplished by using controlled polymerization techniques to synthesize the mimetic copolymers. 3.) To definitively establish the biocompatibility of the mimetic adhesive and potential breakdown products both in vitro and in a living animal model. This will be accomplished in direct contact cell culture experiments with multiple relevant cell lines and by long term analysis of adhesive repaired bone fractures in the animal. Rates of adhesive degradation and resorption will be evaluated both in vitro and in vivo. PUBLIC HEALTH RELEVANCE: An injectable, low-viscosity bone adhesive would improve the clinical outcome for a broad population of orthopedic trauma patients by facilitating more accurate alignment of small bone fragments. Better alignment during bone healing decreases the risk of post- traumatic arthritis.